Results of the study coordinated by researchers from Ospedale Niguarda and the Università degli Studi di Milano, supported by the AIRC Foundation for Cancer Research, published today in THE LANCET Oncology.

A significant recent advance has occurred in the treatment of rectal cancer: the results of the NO-CUT clinical trial, which change and improve clinical practice for this disease, have just been published in the journal THE LANCET Oncology. Rectal cancer affects 700,000 patients worldwide each year, and 340,000 of these die from the disease. In Italy there are more than 14,000 new cases annually, with about 5,000 deaths. These figures alone highlight the urgency of finding new treatments and the importance of the results obtained: in one in four people, in fact, the NO-CUT protocol made it possible to achieve a durable complete remission of the tumor without surgery and without increasing the risk of distant metastases

“Overall,” commented Salvatore Siena, Director of Falck Oncology at Ospedale Niguarda in Milan and Professor of Medical Oncology at the Università degli Studi di Milano, “we can say that the approach validated by the NO-CUT clinical trial represents a significant advance for patients affected by rectal carcinoma and is a milestone in oncology. The data from the NO-CUT study show that when preoperative therapies eradicate the tumor, surgery can be replaced by careful follow-up, thus offering the possibility of cure without the need for an operation. The collected results confirmed the safety of this strategy, which has become an established option in therapeutic guidelines for rectal carcinoma.”

The study involved 180 patients with locally advanced rectal carcinoma, treated with total neoadjuvant therapy — that is, four administrations of systemic oncologic therapy followed by radiotherapy and chemotherapy. Of these, those who achieved a clinical complete response, approximately 25%, were able to avoid rectal surgery without an increased risk of developing metastases in other organs. The NO-CUT study also "has an important translational component: physicians and researchers used advanced diagnostic tools such as circulating tumor DNA analysis (so-called liquid biopsy) and transcriptional profiling of individual tumors. The aim was to identify patients who can benefit from neoadjuvant therapy and a non-surgical approach, or those who do not benefit and should be directed to immediate surgery, thereby avoiding ineffective treatments".

Locally advanced rectal carcinomas — excluding early-stage and metastatic disease — account for about one third of all new cases. Until now, cure has been possible with a multimodal therapy including radiotherapy, systemic oncologic therapy, and rectal surgery. Thanks to the results of the newly published NO-CUT study, surgery can be avoided in one quarter of cases without compromising the possibility of cure.

The study, conceived in 2017 and open to patient enrollment from 2018 to 2024, was promoted by Ospedale Niguarda and Università degli Studi di Milano and conducted at four oncology centers: Niguarda itself (principal investigator Salvatore Siena), European Institute

of Oncology in Milan (principal investigator Maria Giulia Zampino), Veneto Institute of Oncology in Padua (principal investigator Francesca Bergamo), and Papa Giovanni XXIII Hospital in Bergamo (principal investigator Stefania Mosconi). IFOM ETS – The AIRC Institute of Molecular Oncology, Mario Negri Institute for Pharmacological Research, Candiolo Institute and University of Turin contributed to the translational studies and statistics. The study was made possible by the participation of 180 patients with rectal cancer and their families, and by the work of many researchers: medical oncologists, radiation oncologists, surgeons, radiologists, endoscopists, pathologists, psychologists, physicists, biologists, pharmacists, nurses, statisticians, and also radiotherapy, radiology and laboratory technicians, and logistical administrative staff.

NO-CUT was supported by Fondazione AIRC ETS, Fondazione Oncologia Niguarda ETS, and Ospedale Niguarda. The first authors of the publication in LancetTHE LANCET Oncology are joint first authors Alessio Amatu (high-specialty oncologist and head of the Molecular Tumor Board, Ospedale Niguarda) and Giorgio Patelli (oncologist and PhD student, University of Milan, IFOM — Foundation Institute of Molecular OncologyETS – The AIRC Institute of Molecular Oncology and Ospedale Niguarda Hospital); the senior author is Salvatore Siena, Director of the Niguarda Cancer Center and Professor of Medical Oncology at the Università degli Studi di Milano.

PAPER AVAILABLE HERE: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2825%2900542-X/fulltex